Phase II Study of Alternating Sunitinib and Temsirolimus

Sponsor

Dartmouth-Hitchcock Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01517243

Collaborator

(none)

Enrollment

Locations

Arm

148

Duration (Months)

18.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In the past 5 years, treatment for metastatic Renal Cell Carcinoma (mRCC) has focused on agents directed at blocking tumor and vascular growth pathways. Sunitinib blocks the vascular endothelial growth factor receptor (VEGFr) and temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR). Both sunitinib and temsirolimus are FDA approved agents for mRCC. When agents like these are given together, the toxicity increases but they can be given safely, at full doses, sequentially. We hypothesize that alternating these agents will double the progression free survival (PFS) of the agents when given sequentially.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: Sunitinib Drug: Temsirolimus	Phase 2

Detailed Description

SUMMARY: Alternating Targeted Therapy in Patients with Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus

Patients with measurable metastatic renal cell carcinoma (any histology) are eligible. All patients will be treated as outlined below with sunitinib alternating with temsirolimus.

Patients will be treated continuously, until evidence of progression of disease, or for up to two cycles following disappearance of all disease.

A cycle is defined as:

Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Alternating Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus

Study Start Date :

Jun 1, 2010

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alternating Sunitinib and Temsirolimus A cycle is defined as: Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest	Drug: Sunitinib Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Other Names: Sutent Drug: Temsirolimus Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest Other Names: TORISEL®

Arm

Intervention/Treatment

Experimental: Alternating Sunitinib and Temsirolimus

A cycle is defined as: Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest

Drug: Sunitinib

Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest

Other Names:

Sutent

Drug: Temsirolimus

Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest

Other Names:

TORISEL®

Outcome Measures

Primary Outcome Measures

Time to Progression [From the date of randomization until the first documented progression or date of death from any cause.]
To determine the time to progression in metastatic renal cell carcinoma patients treated with alternating targeted therapy

Secondary Outcome Measures

Clinical Response Rate [Every 12 weeks until progression, estimated time frame is 18 months]
To be assigned a status of partial response or complete response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of stable disease, follow-up measurements must have met the stable disease criteria at least once after study entry at a minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Histologically confirmed metastatic renal cell cancer with evaluable disease.
Patients must be at least 2 weeks from their last immunotherapy, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.
Karnofsky Performance Status ≥60%
Life expectancy ≥ twelve weeks
Adequate end organ function:

Cardiac Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by echocardiography (ECHO) . The same modality used at baseline must be applied for subsequent evaluations.

Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study and practicing acceptable forms of birth control
Appropriate Contraception in both sexes
The patient must be competent and signed informed consent.

EXCLUSION CRITERIA

Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.
In patients with a prior history of invasive malignancy, less than five years in complete remission.
Have evidence of significant co-morbid illness such as uncontrolled diabetes, hypertension or active infection that would preclude treatment on this regimen.
Prior treatment with either sunitinib or temsirolimus
Clinically significant gastrointestinal abnormalities
Presence of uncontrolled infection.
Prolongation of corrected QT interval (QTc) > 480 milliseconds - History of any one or more of the following cardiovascular conditions within the past 12 months:

Cardiac angioplasty or stenting
Myocardial infarction
Unstable angina
Coronary artery by-pass graft surgery
Symptomatic peripheral vascular disease
Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)

History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) within the past 12 months.
History of pulmonary embolism or untreated deep venous thrombosis (DVT)within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
Poorly controlled hypertension [defined as systolic blood pressure (SBP) of

≥150 or diastolic blood pressure (DBP) of ≥ 90. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.

Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
Evidence of active bleeding or bleeding diathesis
Hemoptysis within 6 weeks of first dose of study drug.
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug any minor surgeries (i.e. skin biopsy, tooth extraction, etc.) and recovered from all ill effects.
Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to sunitinib or temsirolimus.
Untreated brain metastasis. (Brain metastases that are stable based on radiographic evidence 4 weeks after radiation and/or surgery are permitted).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
2	University of Vermont, Vermont Cancer Center	Burlington	Vermont	United States	05401